ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.592A>G (p.Ile198Val)

gnomAD frequency: 0.00002  dbSNP: rs774629715
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000821306 SCV000962060 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-10-10 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 198 of the PMS2 protein (p.Ile198Val). This variant is present in population databases (rs774629715, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 663439). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt PMS2 function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001024693 SCV001186755 likely benign Hereditary cancer-predisposing syndrome 2018-10-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV004720013 SCV005325891 uncertain significance not provided 2023-12-13 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 11574484)

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